The present invention relates to complexes of proteinaceous material and bismuth used in pharmaceutical preparations useful against inflamed and ulcerated conditions. The complexes (subject to elementary precautions as to toxicity) lend themselves to internal use such as, in particular, by oral administration.
Pharmaceutical preparations intended for oral administration are known wherein a proteinaceous material and a bismuth salt is converted into a variety of compounds, sometimes of the nature of complexes. In most of these processes, the proteinaceous material is broken down drastically into fragments of very much lower molecular weight. In accordance with German Pat. No. 585163 protein is first subjected to fairly drastic digestion with strong alkali to achieve hydrolysis. The hydrolysed proteins are then converted into salts of various heavy metals (e.g. bismuth) and these bismuth salts are then further stabilised by reaction with tannic esters.
In accordance with German Pat. Nos. 588 710 and 655 684 the products are salts of metals such as bismuth and sulfhydrylceratic acid which is not a protein, but an acid formed by the hydrolysis of certain proteins.
German Pat. No. 666 467 relates to metal compounds (e.g. bismuth compounds) produced by coupling reaction between diazotised metal compounds and certain proteins. These products are not complexes at all.
German Pat. No. 101 683 again describes the manufacture of salts of bismuth and acidic degradation products of proteins.
German Pat. No. 202 955 relates to the manufacture of bismuth salts of paranucleic acid. Paranucleic acids are not proteins, but are hydrolysis products of considerably lower molecular weight than that of the proteins from which they are derived.
German Pat. No. 117 269 describes a comparatively drastic reaction which results in the formation of totally insoluble bismuth compounds.
French Pat. No. 577 407 again relates to the manufacture of bismuth salts of nucleic acids. Nucleic acids are not proteins, but are hydrolysis products of lower molecular weight, and the compounds formed are salts and not complexes.
None of the aforegoing preparations which are used i.a. for bacteriostatic purposes have ever been shown to have any efficacy for the treatment of ulcers, in particular gastro-intestinal ulcers. None of these preparations contain water-soluble non-dialysable bismuth protein complexes which are reversably precipitable by alcohol and in which the bismuth is stably bound and not removable by dialysis.
For the treatment of gastro-intestinal disorders, including ulcers, it has been suggested to use commercial bismuth preparations of the type generally referred to as bismuth ammonium citrate (BAC) or occasionally tartrate. BAC commercially available for that purpose is in reality mostly "bismuth ammonium citrate cum pepsin." The preparation thereof is described in various issues of BPC (British Pharmaceutical Codex), e.g. of 1929. Such compositions are also known in the pharmaceutical trade as "Mistura Pepsini et Bismuthi Compositum sine tinctura nucis vomicae et acid hydrocyanicum." Such compositions usually contain cochineal dye or carmine, which contains 50% of the anthraquinone type dye carminic acid, (C.sub.12 H.sub.22 O.sub.13). The other constituents normally present in BAC solutions--notably glycerol or sugar-presumably serve to stabilize the solution. Such compositions were always believed to be mere mixtures of the starting materials. However, the present applicant has in fact discovered (non-published research work) that in the mixing of the ingredients of BAC with pepsin certain complexes (or addition compounds) of protein and bismuth are also formed. However, in those complexes the bismuth is only loosely bound and is removed immediately when subjected to dialysis. It has never been possible to prove for those prior art preparations any efficacy in gastric ulcer therapy statistically significantly better than Placebo.
Protein complexes of bismuth have been known in the literature in the context of using bismuth as a precipitant for proteins. The present invention by way of contrast relates to novel, essentially water-soluble proteinaceous complexes of bismuth.
The conventional treatment of ulcers of the intestinal tract, in particular gastric ulcers has been surgery and/or strict dieting, antacid treatment and rest.
It is an object of the invention to provide improvements in the context of treatment of and prophylaxis against inflammatory conditions and ulcers, in particular ulcers of the gastro-intestinal tract such as peptic and duodenal ulcers.
It is also an object to provide a treatment of gastric ulcers requiring little or no dieting and which is carried out without antacid treatments.